What caused the male mice in Dr. Haim Cohen’s lab at Bar-Ilan University to live 15 percent longer than usual? It was extra doses of a gene called Sirtuin 6, or SIRT6 for short.

And why didn’t it have the same effect on the female mice? Stay tuned for further research from the Israeli team headed by the molecular biologist.

As described in the February 22 online issue of the popular science journal Nature, seven types of sirtuin genes are thought to encode a class of proteins found in every species from single-celled yeast to complex humans. Scientists had previously shown that removing SIRT1 from yeast, worms and flies caused faster aging and earlier death, while transplanting a copy of SIRT1 increased their life expectancy.

Cohen wanted to see the effect of sirtuins in mammals. A 2006 study demonstrated that mice lacking SIRT6 aged more quickly, developing spinal curvature, calcium deficiency, osteoporosis, immune system problems and diabetes. Perhaps, he reasoned, an abundance of SIRT6 would have the opposite effect.

Bar-Ilan graduate student Yariv Kanfi spent more than five years readying a batch of mice to receive extra SIRT6 in Cohen’s lab. In the project’s seventh year, the startling results were noted, with help from pathologists at Hebrew University’s Hadassah Medical School and computational biology by Prof. Ziv Bar-Joseph from Pennsylvania’s Carnegie Mellon University.

“We’ve made a huge evolutionary leap in the transition from yeast cells to mice,” said Cohen.

“We were the first to show that these sirtuin genes regulate lifespan in mammals. The research was conducted in laboratory animals under very sterile conditions. Is this what happens in nature? It’s not clear. The human SIRT6 gene is very similar to that in mice. It could be that drugs designed to activate the gene will have a positive impact on our ability to treat age-related diseases.”

Difference between males and females

Much work remains, as Cohen’s lab tries to figure out why SIRT6 injections had anti-aging effects only in males.

“I’m now researching the gender difference,” says Shoshana Naiman, a doctoral student whose job was to test the protein levels in the mice during the study. “Females have different hormone levels, and that affects metabolism and lifespan. SIRT6 perhaps caused the male mice to be a little more like the females. I’m heading a project to understand exactly how the lifespan extension occurs so we can try to transfer it to humans.”

Bar-Joseph will continue to contribute his analysis of the large amounts of data from the experiments. “We have a technology now that allows us to measure the levels of 25,000 major proteins in the body,” he says. “We will use it to understand how the proteins are rising in the mice Haim looked at ... and to find out how [SIRT6] extends life.”

The mechanisms behind aging are a hotly debated topic these days, Bar-Joseph adds. “This is a very important finding to the scientific community and to the general public.”

In the next round of experiments, Cohen’s team will try to determine exactly which body tissues are most important in the anti-aging process.

“We over-expressed the gene in every tissue, and now we want to see which tissue contributes what to longevity of life,” he explains. “We are also trying to build a system to search for molecules that mimic the effect of the results in mice. If we want to translate this to human therapy, we must find the molecules that activate the protein. Once we have that, we can go to clinical trials.”